Cheating students turn to smart drug for edge in exams
Alexandra Frean and Patrick Foster
Students say they are turning to a powerful prescription drug that is stocked by the Army to keep combat troops alert.
Modafinil, used to treat sleep disorders such as narcolepsy, appears to be overtaking the antihyperactivity medicine Ritalin as the "smart drug" of choice on university campuses.
Drug trials suggest that modafinil, which can be bought on the internet, is highly effective at enhancing short-term memory and enabling users to stay up for extended periods.
But experts say overuse can produce adverse side-effects. Some are also beginning to question why a performance-enhancing drug that is banned for athletes in the Olympics should be allowed for students in exams.
Paul Cooper, director of education at Leicester University, said that, although universities had been aware for some time that students were using drugs such as Ritalin and modafinil to get them through their exams, there had been no proper consideration of whether this constituted cheating.
"As a society we need to ask whether we are happy about people who have no impairments using these drugs to enhance their exam performance – we don't allow it in sport, so why at university? Should we regard these drugs as a pharmaceutical version of the pocket calculator – something that students now rely on in exams as a matter of course? This is a debate that needs to happen." Barbara Sahakian, Professor of Clinical Neuropsychology at Cambridge University, agreed that it was difficult to know where to draw the line. "We've done studies on modafinil. It's very effective and it doesn't have the same side-effects as Ritalin. I've been at meetings where I've been offered modafinil by colleagues to combat jet lag," she said.
"This is one of the first drugs where it doesn't seem to have abuse potential. It seems to be a good enhancing agent with minimal side-effects. The question is what do we do? Should we treat it like coffee?"
If the answer is yes, the next question facing universities may be this: should students be encouraged to take such drugs?
Students have used drugs to boost their study performance in the past. Caffeine and ginseng are traditional favourites. But recently the use of more powerful, restricted drugs, particularly Ritalin, has spread from campuses in the US.
At present the debate within British universities remains focused on the health risks faced by students taking prescription drugs. But students appear not to share these concerns. An undergraduate at Oxford told The Times that he was selling modafinil tablets to other students. "I bought the tablets on a Canadian website but they were produced in India," he said. "I paid less than £1 per tablet and sold them on for £8 to £12 a hit. I made over £3,000 in less than two months. It got even more popular as finals approached."He said that he would get up at 5am, take a tablet and then go back to sleep for an hour. "I'd get up and feel completely refreshed, and I could work all the way through until going to bed at 1am the next morning."
A spokesman for Oxford University said that any student aware of drug dealing should report it to the police. Veronica King, head of welfare at the National Union of Students, said that such dealing may be a sign of the increasing pressures placed on today's students.
Juicing the Brain
Research to limit mental fatigue among soldiers may
foster controversial ways to enhance any person's brain
By Jonathan D. Moreno
Physicians have long tinkered with ways to "improve" the human brain, but as our understanding of that organ's inner workings quickly grows, artificial enhancement is becoming more feasible. Military research is at the forefront of this work, much of it focused on drugs. The goal is to produce a better soldier, but the emerging techniques could just as easily be applied to any individual. The military wants to juice up personnel's brains because the human being is the weakest instrument of warfare. Although for centuries astonishing and terrifying advances have been made in the technology of conflict, soldiers are basically the same. They must eat, sleep, discern friend from foe, heal when wounded, and so forth. The first state (or nonstate) actor to build superior fighters will make an enormous leap in the arms race. In the short run, researchers are trying to devise aids that would overcome a person's inherent limitations, such as mental fatigue. Long-term results could lead to individuals everywhere who are tireless, less fearful or even better speakers.
Sleepless in Battle
Reducing human error caused by mental fatigue is crucial because death by "friendly fire" is a shockingly frequent occurrence. These tragic mistakes can partly be attributed to the sleep deprivation that accompanies lengthy deployments. An investigation into a 2002 incident in which two American pilots accidentally killed four Canadian soldiers and injured eight others in Afghanistan provided an unexpected glimpse into the U.S. Air Force's interest in sleep. Unnoticed by many, the pilots' attorneys in the resulting court-martial cases pointed out that their clients had been taking Dexedrine, sometimes called the go pill, otherwise known as speed. It was alleged that amphetamines such as Dexedrine are commonly prescribed to keep pilots alert for 30-hour missions, even though questions have been raised about safety. Use of such drugs can also lead to dependency.
The air force is considering alternatives to amphetamines, in particular a medication that has also gained the attention of long-distance business travelers: modafinil. Marketed as Provigil, it was approved by the Food and Drug Administration in 1998 to treat narcolepsy and to help control sleep disorders associated with diseases such as Parkinson's, Alzheimer's and multiple sclerosis. Modafinil is not a traditional stimulant; rather than bombarding various parts of the brain with arousal signals, it apparently nudges the brain toward wakefulness through specific pathways, perhaps by increasing serotonin levels in the brain stem. The precise mechanism is still not well understood.
The temptation for healthy people to use such a drug is tremendous; some individuals report that a dose leaves them as refreshed as a short nap. Frequent fliers already get prescriptions for the stuff, and it is sure to be the next craze on college campuses among students who want to pull all-nighters or just be able to party hearty for days. Long-distance truck drivers are also obvious candidates for use and, perhaps, abuse.
Workers who shift from day to night schedules and back again are also interested. They often complain of drowsiness during the workperiod and insomnia when they want to sleep. The Air Force Office of Scientific Research and Cephalon, Inc., in Frazer, Pa., sponsored a study by Harvard University and the University of Pennsylvania in which 16 healthy subjects were treated like shift workers: they were deprived of sleep for 28 hours, then obliged to sleep from 11 A.M. to 7 P.M. for four days and to stay awake those nights. The subjects on modalert did far better on cognitive tests than those on a sugar pill. Double-blinded, placebo-controlled studies have shown that some subjects can stay awake for more than 90 hours.
A few news outlets have made unconfirmed claims that American soldiers were using modafinil on the way to Baghdad in 2003. That would not be surprising. Minimizing the need for sleep has been a holy grail for war planners since time immemorial. Guards at China's Great Wall chewed an herb containing ephedrine; Incan fighters munched on coca leaves; 19th-century Bavarian officers gave their men cocaine; soldiers from several countries used amphetamines during World War II; and, of course, armies consume countless tons of caffeine and nicotine. French soldiers took modafinil in the first Gulf War, and the Guardian newspaper reported in 2004 that the U.K.'s Ministry of Defense had purchased 24,000 tablets of the drug.
Despite the interest in modafinil, questions persist. Does it mask natural sleep needs but fall short in keeping people as functional as they think they are? This could be critical for pilots and soldiers, who should not overestimate their readiness. After prolonged use, the endocrine and immune systems may be compromised by lack of sleep, too.
Military scientists are examining the safety issues. One researcher at the air force's Brooks City-Base in San Antonio told Pentagram, an online newsletter, that "all indications say modafinil is a safer drug, but we don't know that for sure." But even if the compound proves safe in terms of sound judgment in combat, what about the effects down the road for people who have been on and off the drug for years? The long-term risks associated with sleep deprivation are not well understood either. Evidence indicates that during sleep, memory and learning are consolidated and that the brain refreshes its store of energy.
Studies have shown that people who sleep only four hours a day for an extended period have an increase in insulin resistance, a prediabetic symptom. But without a proven explanation for the purpose of sleep, it is hard to assess the downside of doing without, other than the obvious discomfort that nonsleepers experience--the attendant loss of concentration and the increased accident risks.
An intervention that minimizes the need for sleep yet maintains cognitive capacity would be a significant advantage for a military force. Infantrymen commonly subsist on three or four hours of sleep nightly for weeks. Special Forces personnel may be awake for several days during search and rescue operations. The Defense Advanced Projects Research Agency (DARPA) is spending $100 million in grants on "prevention of degradation of cognitive performance due to sleep deprivation." DARPA's Defense Sciences Office has stated that "if you can prevent bad decisions from being made during sleep deprivation, you can dominate the battlefield." It is also interested in how to reverse losses that might occur during sleep deprivation and whether researchers can "expand the available memory space, so that people can retain cognitive function under tremendous stress and sleep deprivation."
The military effort includes investigation of another class of drugs, the ampakines, which show some promise in treating dementia and symptoms of schizophrenia by improving cognition when used with antipsychotic medication. Clinical trials have not found therapeutic value, but results from a company-sponsored study at Wake Forest University using an ampakine drug in sleep-deprived rhesus monkeys were encouraging. The monkeys' performance was reduced 15 to 25 percent when sleep-deprived, and reaction times doubled. But a single dose of Ampakine CX717 eliminated their performance deficit and sleep deprivation changes. An unpublished human trial sponsored by the company that makes CX717 reported that 16 men deprived of a night's sleep did better on memory and attention tests after taking the drug. The scientist who conducted the study said, "We didn't see any adverse events."
How Far Can We Go?
Military work is only the beginning of intense efforts to control sleep-wake cycles. There is a multibillion-dollar demand from civilians who wish to sleep only when they want to sleep. The neuroscientific key lies in a part of the hypothalamus called the suprachiasmatic nucleus (SCN), the brain's biological clock. About the size of a pinhead and nestled deep within the brain, the SCN, composed of 20,000 neurons, acts as the pacemaker for circadian rhythms in mammals. If the SCN is cut or removed in animals, their sleep-wake cycle can be profoundly disturbed. And when people are deprived of light, the SCN runs on a 25-hour clock; for some reason that is our innate length of a single day, which helps to explain insomnia and other sleep disorders in those who are blind. Though subject to some variation, the clock can be reset by exposure to light signals transmitted from the retina, which is why we can function on a regular 24-hour cycle.
There are very few hard data showing that prolonged sleep deprivation has truly deleterious effects in humans, according to Harvard neurobiologist Jerome Groopman. Yet University of Pennsylvania researcher David Dinges has raised provocative questions about Boeing Company's plans for a jetliner that would fly around the earth and need to land only once in 20 hours: How should the crew sleep, if at all? What are the rules that apply to sustained work on flights like that? As Dinges says: "Now is the time to have an open and frank discussion on how far we will go as a culture. What are our priorities? How regularly do we want to manipulate our brain chemistry? What are the limits?"
Some insights may come from the animal world. Dolphins seem to keep parts of their brains awake to control their breathing and guide them to the surface for air while the rest of their brain is allowed to sleep. Otherwise they would drown. Positron-emission tomographic (PET) scans are beginning to reveal how their brain architecture accomplishes this feat. If the mechanism can somehow be simulated safely in human brains, it will be hard to keep the method out of the hands of civilians eager to get an edge in a competitive world.
Electricity and Magnetism
Another approach to enhancing cognitive abilities may be electrical stimulation of select brain centers. Physicians at the Rehabilitation Institute of Chicago found that when they implanted electrodes in the motor cortex of stroke victims, patients regained about 30 percent of lost function as compared with 10 percent for other patients. Although the approach is not perfect, the gains for those whose arms had for years hung limply at their sides were wonderful. Some stroke patients with speech difficulties experienced improvement, too. Unfortunately, the doctors do not know exactly why the added electricity works.
An intriguing question is whether electrical stimulation might help uninjured people exceed their normal intellectual capacities. One technique being explored is direct-current (DC) polarization. At a 2004 Society for Neuroscience meeting, researchers from the National Institutes of Health reported that a tiny amount of electricity delivered to the brain through an electrode on the scalp produced measurable improvement in verbal skills. They asked volunteers to name as many words as possible that began with a certain letter. The subjects showed about a 20 percent improvement when the current (two thousandths of an ampere, far less than that needed to run a digital watch) was on.
Because the current ran through the prefrontal cortex, the researchers speculated that the firing rate of neurons was increased, activating cells involved in word generation. The tiny charge seemed to have no deleterious effects, other than to leave certain individuals with an itchy scalp. Moreover, the fact that the technique does not involve surgery makes it more practical than implanted electrodes.
Another noninvasive technique is transcranial magnetic stimulation (TMS). A magnetic coil is placed above the head, and magnetic pulses pass through the cortex. Different kinds of pulses can alter the firing rate of different sets of neurons. Volunteers complain only about a sensation of tapping on the skull as scalp muscles contract and about a popping sound from the magnetic coil.
The therapeutic goal for DC polarization and TMS is to treat patients with stroke or dementia. TMS seems to target specific brain regions more effectively, but DC polarization appears to carry less risk of inducing seizures. Of course, the long-term effects of frequent exposure to electrical or magnetic stimulation are unknown. Nevertheless, DARPA has awarded research grants to explore whether neurostimulation can improve impaired cognitive performance in confusing battle circumstances or to offset sleep deprivation, perhaps through helmets that deliver the tiny impulses needed.
Like so many potentially brain-enhancing technologies, neurostimulation can easily be oversold. Given how much we value cognition, however, even a modest improvement would be considered important by many people. Long-term problems for military personnel might be hard to identify and could seem worth the risk for even a marginal gain in mental agility in life-or-death situations. As neuroscientist Mark E. Huang of the Rehabilitation Institute of Chicago told the press in 2004: "There are many possibilities that have to be answered ethically. If you want to learn a new language, potentially the stimulator might help. Would I recommend you do it for that purpose? No. But down the road, who knows? Obviously the sky's the limit, and we're still in the infancy stage."
Possibilities for mind enhancement indeed abound. A distinguished team of U.S. researchers reported in 2005 that a gene called stathmin, which is expressed in the amygdala (the seat of emotion), is associated with both innate and learned fear. The researchers bred mice without the gene and put them in aversive situations, such as giving them a mild shock at a certain point in their cage. Normal mice exhibited traditional fear behavior by freezing in place, but the altered mice froze less often. And when both types of mice were put in an open field environment--an innately threatening situation--the mice without stathmin spent more time in the center of the field and explored more than the control mice.
Do individuals who have lesser stathmin expression exhibit less fear? It is unlikely that there is a one-to-one correspondence, because humans are far more psychologically complex than mice, capable of modifying their genetically programmed behavior. Yet it is not difficult to imagine that a military official who overestimates the significance of genetic information will someday propose screening Special Forces candidates, or even raw recruits, for the "fear gene." Indeed, a few years ago the Burlington Northern Santa Fe Railway Company had to pay $2.2 million to employees who had been secretly tested for a gene associated with carpal tunnel syndrome, even though the scientists who developed the testing technique said it could not work for that purpose. The company was trying to see if the workers' medical claims were attributable to their jobs or their genes.
If DNA testing for a fear gene is both scientifically and ethically dicey, what about setting out to create people who lack that characteristic? Would breeding humans without stathmin or other genes associated with fear reactions engender more courageous fighters? Would parents sign on for such meddling if they harbored ambitions for a child capable of a glorious military career or just didn't want to give birth to a "sissy"? One problem, however, is that fear or its functional equivalent is one of those ancient properties exhibited by just about every animal. It surely has tremendous survival value. Removing it would be deeply counterevolutionary and would almost certainly generate numerous unintended and undesirable consequences for the individual, let alone thrust humans headlong into a fierce debate about whether enhancing ourselves has gone too far.
Proponents of such artificial enhancements argue that the changes may not be artificial at all. Is there even a valid distinction, they ask, between artificial and "natural" enhancements such as exercise and discipline? Aren't we just trying to gain whatever advantages we can, as we have always tried to do, or are these techniques cheating nature? Can we manage the consequences, or are the risks for the individual and for humanity too great?
These questions are part of an ongoing argument about whether we should use new discoveries in neuroscience and other fields such as genetics to improve ourselves, our descendants and perhaps even the species. If it becomes acceptable to enhance civilians, then it would be hard to explain why national security agencies should be barred from giving war fighters an edge. And if it is not acceptable to enhance civilians, a special case might still be made for tuning up military personnel.
National research on enhancement technologies will require the close involvement of advisory bodies with members both in government and outside it, with as much transparency as possible. Whereas some general principles should be articulated and become part of our regulatory framework, much of the hard work will have to be done on a case-by-case basis.
As Dinges notes, the debates are ones we haven't had. Libertarians would argue that government regulation would be overreaching, conservatives would worry about changing human nature, and liberals would worry about inequitable access to whatever advantages neuropharmacology might confer on those who are already relatively well off. All these views deserve to be aired, and the discussion needs to be moved onto our national policy agenda.
Sprinter likely to lose gold medals
after positive test
MONTE CARLO - American sprinter Kelli White is likely to be stripped of her 100m and 200m world championship gold medals after confirmation yesterday that her B sample was positive.
White tested positive for the banned stimulant modafinil in a urine test after her 100m victory at the world athletics championships in Paris in August.
"I can officially confirm it [that the B sample is positive]," said Nick Davies, a spokesman for the International Association of Athletics Federations, in Monte Carlo.
The 26-year-old sprinter told the association that she used the substance to treat a medical condition which ran in her family.
She also said she believed she did not have to declare the modafinil because it was not on the list of banned substances.
Because of that, White has escaped a two-year ban, although modafinil will be named in the list of the World Anti-Doping Agency as of January 1.
In August, the association ratified the agency's world anti-doping code, which harmonises efforts to catch cheats.
American hurdler Chris Phillips, who finished fifth in the 110m hurdles, also had a positive B sample for modafinil.
Both cases have now been referred to the United States Anti-Doping Agency by the association, and it is expected to hand them over to the world agency.
* A leading scientist says the anti-doping agency is close to unveiling tests that will detect "gene doping".
The move follows mounting concern that gene therapy, used to treat chronic medical conditions such as muscular dystrophy, is being misused by unscrupulous athletes and coaches.
Professor Geoff Goldspink, of the University College in London, speaking on the sidelines of the four-day IOC medical congress in Athens, said testing technology was "almost there - we can already detect illicit DNA and introduced gene products".
Goldspink has been compiling a report which is expected to be handed to the world agency in Lausanne in a fortnight.
Congress delegates warned that gene doping presents a "clear and present danger" and that international sports authorities are facing the next generation of sports cheats.
"We can put genes into mice and create Arnold Schwarzenegger mice," Goldspink said.
"If it can be done on mice it can be done on humans."
Laboratory mice had shown that gene transfer could lead to a 25 per cent increase in muscle mass within two weeks, he said.
"It's inevitable that we will have this kind of doping - if we don't already have it.
"Once the technology exists for medical use, disreputable people will be putting the stuff in athletes."
Scientists at the congress said present testing methods aimed at catching athletes using banned substances such as anabolic steroids or amphetamines were unable to catch gene cheats.
Wakefulness Finds a Powerful Ally
By ANAHAD O'CONNOR
Laurie Coots, a marketing executive who flies to meetings in other countries twice a week, spent years trying to conquer sleepless nights and chronic jet lag. But nothing worked, she says, and every day was a struggle to stay awake.
"It was debilitating," said Ms. Coots, 46, who is from Los Angeles. "I couldn't give an effective presentation because I was always shaky and nervous from being amped up on caffeine and stimulants."
Then she found modafinil, a small white pill that revs up the central nervous system without the jitteriness of caffeine or the addiction and euphoria of amphetamines.
"Without it my life would not be possible," she said.
Since 1998, modafinil, made by Cephalon and sold under the brand name Provigil, has quietly altered the lives of millions of people. No one knows exactly how it works, but sales of the drug are skyrocketing.
People who take it say it keeps them awake for hours or even days. It has been described as a nap in the form of a pill, making most users feel refreshed and alert but still able to go to bed when they are ready. And because its side effects are rarely worse than a mild headache or slight nausea, experts fear that it has rapidly become a tempting pick-me-up to a nation that battles sleep with more than 100 million cups of coffee a day.
Few numbers are available, but experts say that as modafinil grows more widely available, it is becoming a fixture among college students, long-haul truckers, computer programmers and others determined to burn the midnight oil. Some worry that an array of common disorders, like diabetes and sleep apnea, will go undiagnosed if doctors dole out Provigil instead of seeking the underlying diseases that cause fatigue.
In a culture of 24-hour stores, graveyard shifts and coffee shops on every corner, modafinil might also pose a more subtle danger: to the countless Americans in search of an extra edge, modafinil could be a cure for sleep.
"This drug enables us to be that much more workaholic and that much more obsessed with accomplishments and productivity, and I think our society is already extreme along those lines," said Dr. Martha J. Farah, director of the Center for Cognitive Neuroscience at the University of Pennsylvania. "The natural checks on that tendency, like needing to go to bed, are being rolled back by modafinil."
To the extent that modafinil becomes the latest lifestyle drug, as ubiquitous as Viagra, scientists warn that cutting back on sleep, even by one hour a night, can have long-term neurological and cardiovascular effects that are only now being recognized.
"It's almost fortuitous that at the same time that this drug has come out, we have increasing mounds of data showing that sleep is a restorative, protective health process," said Dr. Neil B. Kavey, director of the Sleep Disorders Center at Columbia Presbyterian Medical Center. "It affects performance, blood pressure, heart rate, insulin, various hormone secretions. No matter what medications come out that make sleep seem like a waste of time, we know that the sleep-deprived state is a bad one to be in."
Discovered by French researchers in the late 1970's, modafinil went on the market in the United States in 1998 as a treatment for narcolepsy, a severe sleep disorder. Earlier this year, the Food and Drug Administration broadened its approved uses to include obstructive sleep apnea, a narrowing or blockage of the airways, and sleeping problems caused by shift work. An effort by Cephalon to have the drug approved for a third indication, excessive sleepiness from any cause, was rejected.
But the three conditions modafinil is approved to treat make up only a fraction of its total uses. According to Cephalon, based in West Chester, Pa., 90 percent of all prescriptions for the drug are for "off-label" uses, including fatigue, depression, attention deficit hyperactivity disorder, and sleepiness caused by other prescription medications.
In the last year, six American track and field athletes have tested positive for the substance, which is on the United States Olympic Committee's list of banned stimulants. One group of scientists is testing its effectiveness as an appetite suppressant in people who are overweight. And a government-financed study found that it blunts the high produced by cocaine, making it a promising treatment for addiction.
"The off-label use of this drug is staggering," said Dr. Eric Heiligenstein, a psychiatrist at the University of Wisconsin who studies substance abuse by teenagers.
"This is a very clean drug that affects all the things that help people with their cognitive functioning," he said. "The main barrier to more widespread use is that it's expensive, which will change as more insurance companies start to cover it."
For doctors, modafinil's biggest lure is its safety profile. It was used in France for several years without reports of major problems before reaching the United States. In clinical trials, only about 1 percent of people complained of side effects, including nausea, mild headache and nervousness.
But scientists point out that as with any drug, more serious side effects could appear as modafinil is used more widely.
"I'm not aware of any terrible outcomes, but I don't think there have been enough long-term studies of modafinil to rule out all dangers," said Dr. Jerome M. Siegel, chief of neurobiology research at the Veterans Affairs Greater Los Angeles Healthcare System. Total worldwide sales of Provigil soared above $290 million in 2003, up from $207 million in 2002. Marc Goodman, a pharmaceutical analyst at Morgan Stanley, expects that figure to reach $409 million this year. More than 90 percent of that revenue, he said, will come from sales in the United States alone.
"If you look back before the drug was launched, no one would ever have believed it would be this big," Mr. Goodman said. "Everyone viewed narcolepsy as the market and didn't appreciate the benign side-effect profile and how that would play into off-label uses."
Between 2002 and 2003, Provigil's share of the stimulants market grew by 39 percent, according to IMS Health, a company that tracks the pharmaceutical industry.
In the near future, modafinil could find its way into even more medicine cabinets. Mr. Goodman said it was likely that Cephalon's patent for the compound would be challenged by several drug companies seeking to market generic versions. If they succeed, it would increase the availability of modafinil and almost certainly drive down the price of a monthly supply, which is now $120 or more.
Cephalon is working on Provigil's successor, a longer lasting version the company calls Nuvigil. It also hopes to win approval for modafinil as a treatment for children with attention deficit disorder, the most commonly diagnosed behavioral disorder of childhood. Some experts think this would open the door to the drug becoming even more of a household name.
Of all the questions surrounding modafinil, perhaps the most intriguing is how it works. After more than two decades of research, scientists are still trying to figure out just how it manipulates the brain.
"It is amazing that this drug has become so widely used without any real understanding of the basic science behind it," Dr. Siegel said.
Researchers know that modafinil is distinctly different from conventional stimulants, which ramp up arousal and set off a flurry of activity throughout the brain. Such stimulants, like cocaine and amphetamines, for example, produce wakefulness but also produce a high and can lead to dependence. Modafinil appears to steer clear of those side effects by aiming at specific structures and chemicals.
One neurotransmitter that is thought to be involved is dopamine, which mediates the reward pathways in the brain, producing euphoria, pleasure and addiction. Cocaine and amphetamines cause a surge in dopamine levels, while modafinil's effects are much weaker. A study of animals lacking a protein that helps process dopamine found that they did not respond to modafinil.
Dr. Thomas Scammell, an associate professor of neurology at Harvard's medical school who was involved in preclinical trials of the drug, believes that modafinil may home in on a single poorly understood dopamine circuit that is specific for wakefulness, while amphetamines and other stimulants activate all three of the brain's dopamine pathways, including those involved in addiction and locomotor activity. That selectivity, he said, might be crucial in modafinil's lack of unwanted side effects.
"I think it is a subtle enough drug that it doesn't just activate everything," he said.
Modafinil's impact on the brain is so subtle that brain scans of people who have taken it hardly register any change in activity at all. Give them amphetamine or a drug for Parkinson's disease, Dr. Scammell said, and "the changes in brain function are spectacular," but give them modafinil, and they show little more than ordinary wakefulness.
Most scientists suspect that at least three other transmitters are involved. One of them, histamine, is responsible for the sleep-inducing effects of many cold and allergy medications. In a study last month, Dr. Siegel, who is also a professor of psychiatry and biobehavioral sciences at the University of California at Los Angeles, found that histamine in the brain helps control consciousness.
In the rapid-eye-movement stage of sleep, lower levels of norepinephrine and serotonin keep the body still, producing the characteristically slack muscle tone of sleep. Lower levels of histamine, however, specifically reduce consciousness and awareness. In studies on animals last year, Japanese researchers found that modafinil releases histamine. French researchers this year found that it elevates levels of norepinephrine. And a smaller number of scientists suspect minor involvement by orexin, a substance that is severely depleted in narcoleptics.
Several researchers, including Dr. Siegel, have proposed a unified theory suggesting that all these chemicals are necessary for modafinil to take effect.
"Many things have to work together to achieve alertness," he said. "Modafinil might activate dopamine, which then activates norepinephrine, which then activates histamine, for example. But we still want to know where the initial action is."
Scientists think that the chain of reactions set off by modafinil leads to the hypothalamus, a small structure embedded in the forebrain that controls the body's hormones and regulatory functions. One part of the hypothalamus, known as the ventrolateral preoptic nucleus, appears to act as the body's sleep generator. When it is active, it produces a chemical, GABA, that inhibits the firing of cells involved in wakefulness and arousal. Scientists suspect that by increasing norepinephrine levels, modafinil may block the region from promoting sleep.
Just next door, in the posterior hypothalamus, are bundles of thousands of neurons that produce histamine. Damage to this region, scientists have found, causes excessive sleepiness. Dr. Rod Hughes, senior director of scientific communications for Cephalon, thinks the histamine center may generate wakefulness, counteracting the effects of its sleep-inducing neighbor. Modafinil might increase output in this region, coaxing a tired body into switching on its natural alertness system.
Some scientists say that regularly manipulating this system to skimp on sleep could have dire consequences. Studies have shown that chronic sleep deprivation damages health, weakening the immune system and increasing the likelihood of illness. It is also associated with a shorter life span.
But other experts counter that Americans will continue to cut back on sleep, whether they have modafinil or not. The toll of this deprivation has been visible for years on the nation's highways, where impaired judgment from sleepiness is blamed for about 100,000 accidents a year. Lack of sleep is also believed to have played a role in the space shuttle Challenger disaster, the nuclear meltdown at Chernobyl and the Exxon Valdez oil spill.
"In terms of error rate, 18 hours of no sleep, which many of us regularly do, is equivalent to a blood alcohol level of about .05," said Dr. Ronald Chervin, who was involved in clinical trials of modafinil and is the director of the University of Michigan sleep disorders center. "Twenty-one hours of no sleep is equivalent to a blood alcohol level of .08, which is illegal in many states."
If someone is falling asleep on the highway, and has no other option than driving to work, Dr. Chervin said, "I think many sleep experts would give that patient modafinil, and I think many do."
Dr. Farah, at the Center for Cognitive Neuroscience, is more concerned about the people who are taking modafinil simply so they can get ahead at work or finish a term paper. As it becomes more and more popular to use it for those reasons, she said, people might feel they have to take it just to seem as if they are performing normally.
"It would be a shame for a generation of young adults to come of age believing that the only way they can take on a challenging project is with some kind of pharmacological help," she said. "It's quite possible that modafinil will be the next Ritalin on campus, something that kids go off to college with. If it is widely used for A.D.H.D., then it will probably end up being readily available to the undergraduate masses."
Pills provide brain boost for academics
Some academics use 'smart drugs' to sharpen
their performance. Tony Tysome explores the issues
Feeling under intense pressure to improve your performance at work? Fatigued by the growing demands of a 24/7 society? These are occupational hazards affecting many of today's academics.
But the suggestion that an individual's performance can be improved, and tiredness overcome, simply by popping a pill can shock even those academics who have studied the effects of so-called smart drugs.
Barbara Sahakian, professor of neuropsychology at Cambridge University, was taken aback when a colleague offered her a dose of Modafinil - a "wakefulness" drug prescribed to people suffering from various sleep disorders - as she arrived in the US, jet-lagged, to present a paper at a conference.
Having discovered in her own research how the memory and concentration of healthy people can be improved with the use of Modafinil, Professor Sahakian knew that the drug could potentially help her.
As a matter of principle, she declined the offer. But the incident, along with a similar one at a conference in the Netherlands, made her realise how smart drugs are gaining currency in the global academic community.
She said: "I was intrigued to realise that there are academics who take them on a regular basis. It appears to herald the use of these drugs more generally by people who want something to enhance their academic performance."
The benefits and side-effects of various drugs derived from methylphenidate, commonly used to treat attention deficit hyperactivity disorder (ADHD), have been well documented since the 1960s. More recently, research in the US into the most well-known brand, Ritalin, has found it being used by schoolchildren and undergraduates to improve their levels and periods of concentration and help them perform better in exams.
Debate over the safety, ethics and practicalities of using smart drugs such as Ritalin to enhance academic performance has intensified as a new generation of drugs that appear to have few if any serious side-effects have come on to the market. As well as Modafinil, the latest developments include other ampakines - developed to treat conditions such as Alzheimer's and Parkinson's disease, but also found to generally improve cognitive functions including learning and memory.
Arguments by some academics that taking these drugs is no worse than downing several cups of strong coffee have been countered by concerns that children or employees could be coerced into taking them in an increasingly results-driven culture in schools and the workplace. There are also warnings that some of these drugs are so new that the long-term side-effects are not known.
Paul Cooper, professor of education at Leicester University, who has been studying ADHD for the past 13 years. He said he has anecdotal evidence of parents obtaining Ritalin over the internet to give to their children without prescription.
He sees this as part of what he calls the "democratisation of science", which is helping to spread the use of smart drugs. Availability, combined with performance pressures in today's society, make it almost inevitable that some academics and students will turn to using them, he suggested.
"If you look at our culture today, people will go to all kinds of lengths to gain an educational advantage - from buying houses to get into a particular school's catchment area to resorting to plagiarism at university. If people have a certain way of thinking, they will be sorely tempted to use drugs to enhance their academic performance," he said.
Professor Cooper hopes to win funding to conduct a study into students' attitudes towards the drugs. He said: "I suspect that for some the only thing that would deter them from taking them is the fear of side-effects."
No major studies have yet been conducted in the UK to discover the extent to which smart drugs are being used by academics or students. But some academics contacted by The Times Higher were surprisingly open to the idea of taking them.
Stuart Derbyshire, senior lecturer in psychology at Birmingham University, said: "If it was possible to enhance cognition by taking drugs that were safe and without side-effects, then why would anyone not take them? Such drugs would be welcome."
Nick Bostrom, director of the Future of Humanity Institute at Oxford University, said the development of the drugs for cognitive enhancement purposes should be encouraged and could benefit elderly academics.
He said: "One 100mg dose of Modafinil can be obtained for £1.80 - approximately what it costs to buy a cup of coffee at Starbucks. A 100mg dose for enhancement purposes would be enough for one working day. This is a trivial price to pay."
Hazel Biggs, professor of medical law at Lancaster University, said it could be argued that there was little difference between students drinking caffeine drinks to stay up all night to revise and taking smart drugs.
But she warned that this could give rise to some significant legal questions for universities and employers. She said: "If students use smart drugs to enhance their performance and get a good university degree there could be a legal question when they get a job. If they find they are unable to cope at work without the drugs it could be argued that they have in effect falsified their qualifications, which is a criminal offence."
Several academics also warned of the potentially harmful long-term side-effects of taking non-prescribed smart drugs.
Dave Woodhouse, director of the Cactus Clinic in the School of Social Sciences and Law at Teesside University, said: "There is evidence to suggest that continual use of these drugs over a period of years can prove detrimental to cognitive functioning and, consequently, future academic success. The analogy with sport is useful here: is immediate success worth the potential physical and mental degeneration in later life?"
Steven Rose, emeritus professor of biology at the Open University, said smart drugs raised serious questions for society as well as higher education.
He said: "We live in a pharmacological culture that is likely to take the attitude that if you take drugs to stay awake all night or improve sex, then why not take them to improve your performance in exams?
"We need to think through the implications of that as a society. We are used to dealing with nicotine and alcohol, but we are now facing questions that we are not well equipped to deal with."
TOP FOUR TYPES OF SMART DRUG
Four types of drugs currently on the market or under development have emerged as the main contenders to become the smart drugs of choice for academics or students seeking to enhance their cognitive capabilities. Each has been found to aid concentration and memory among healthy takers.
- Methyl-phenidate has been around since the 1960s. Cost: 60 x 10mg tablets can be obtained on the internet for about £40 (67p per pill).
Popular brand name: Ritalin
Used to treat: Attention deficit hyperactivity disorder.
Known possible side-effects: Increased blood pressure, aggression, dizziness, sleep problems, nausea.
- Modafinil, an ampakine, has been developed and prescribed over the past seven years.
Cost: 30 x 100mg tablets can be obtained on the internet for about £43 (£1.43 per pill).
Popular brand name: Provigil/ Alertec.
Used to treat: Narcolepsy and other sleep disorders.
Known possible side-effects: Anxiety, headaches, nausea, mood swings, nervousness.
- Other ampakines have come on to the scene only in the past two to three years.
Cost: Unknown as these drugs are still in development.
Used to treat: Alzheimer's disease, Parkinson's disease, schizophrenia, ADHD.
Known possible side-effects: In most cases none, although some drugs have been found to cause cases of nausea, headaches and impaired memory.
- Nicotinic Alpha-7 Agonists - the very latest smart drug.
Cost: Unknown as still in development.
Used to treat: Alzheimer's disease and schizophrenia.
Known possible side-effects: No serious side-effects found so far.
'NO EVIDENCE OF SERIOUS RISK'
No convincing argument has yet been made against the use of smart drugs to enhance academic performance, according to Arthur Caplan, professor of bioethics at the University of Pennsylvania.
Professor Caplan, one of higher education's most vocal def-enders of smart drugs, told The Times Higher that worries about safety were no different from normal concerns about any new product or innovation.
"If these drugs really do have harmful side-effects, then I would argue that people in the US and the UK would be unlikely to use them. Since some of these drugs have been around for some time, there doesn't appear to be any evidence that they pose a serious risk," he said.
Professor Caplan acknowledged that there could be an issue over some people such as children feeling coerced into using smart drugs. But he added: "If you are talking about voluntary choice by reasonably competent people, I find it difficult to see in principle why using smart drugs to enhance your capability is bad. I find it laughable when people argue that it's unnatural when we are using devices such as computers and cellphones to enhance our capabilities almost every minute of the day."
Lots of academics and students are already using smart drugs, he claimed.
"The notion that we are getting on to a slippery slope will not inhibit anyone from using anything that they think will give them an edge," he said.
'I WOULD CONSIDER USING THEM MYSELF'
Sarah Chan, a research fellow in bioethics at Manchester University's School of Law, is one of several academics who told The Times Higher they were open to the idea of using smart drugs to boost their academic performance.
"If it were cheaper and more convenient to obtain the current generation of smart drugs, I would certainly consider using them myself," she said.
And she added: "Who among us has not, while struggling to remember an elusive fact, wished for a better memory, or berated ourselves for an inability to concentrate, cudgelling our tired brains to function?
"These drugs might, at the very least, be an improvement on caffeine, the current mental stimulant of choice for many students and academics."
Dr Chan argued that there is nothing morally wrong with using smart drugs to enhance brainpower and said weighing up the benefits and possible risks was a matter for the individual.
She said: "Why should it be wrong to strive to better ourselves? Our capacity for conscious thought and for reason - our ability to observe, consider, interact with and perhaps shape the world around us - is part of what we value most about ourselves. Surely we ought to welcome the means to improve it, be that through better education, tools such as computers or the use of pharmaceutical agents?"
Fears that the cost of smart drugs could create an "unenhanced underclass" who could not afford them ignores the potential benefits to human advancement as a whole, she suggested.
"The solution is to 'level up', to attempt to widen access to technology rather than restrict it. We should not spurn the benefits of smart drugs on the grounds that some cannot enjoy them. Instead, we ought to be making it possible for everyone to take advantage of these benefits - or even encouraging them to do so," she said.
Cephalon Files New Drug Application for NUVIGIL(TM)
Cephalon, Inc. announced today that it has filed a New Drug Application (NDA) with the U.S. Food and Drug Administration seeking approval to market NUVIGIL(TM) (armodafinil) Tablets [C-IV] to improve wakefulness in patients suffering from excessive sleepiness associated with narcolepsy, shift work sleep disorder (SWSD) and obstructive sleep apnea/hypopnea syndrome (OSA/HS). NUVIGIL is a single-isomer formulation of modafinil, the active pharmaceutical ingredient contained in PROVIGIL® (modafinil) Tablets [C-IV].
The NDA is based on positive results of four double-blind, randomized, placebo-controlled studies of NUVIGIL in patients with excessive sleepiness associated with either narcolepsy, SWSD or OSA/HS. The data in this filing show that the primary endpoints of all studies were met and suggest that NUVIGIL is differentiated from PROVIGIL.
"This is the third of five FDA approvals that we will be pursuing over a 15-month time period," said Dr. Paul Blake, Executive Vice President, Worldwide Clinical Research & Regulatory Affairs at Cephalon. "Cephalon is a pioneer in developing compounds for improving wakefulness, and this on- schedule filing allows us to reinforce our leadership position in the treatment of disorders of sleep and wakefulness," added Dr. Blake.
About the Clinical Studies
In four, 12-week studies, daily doses of 150 and 250 milligrams of NUVIGIL or placebo were administered to approximately 1,000 patients with excessive sleepiness associated with either narcolepsy, OSA/HS or SWSD. The primary endpoints in all studies were measures of objective sleep latency (Maintenance of Wakefulness Test or Multiple Sleep Latency Test) and the physician rating of Clinical Global Impression-Change. In each study, patients treated with NUVIGIL showed a statistically significant improvement on both primary endpoints compared to placebo (all p values <0.05). Moreover, recordings and patient diaries showed that compared with placebo, NUVIGIL did not disturb patients' normal sleep schedule.
In these Phase 3 studies, NUVIGIL was generally well tolerated, with a safety profile consistent with that observed in studies of PROVIGIL. The most common adverse effects observed included headache, nausea, dizziness, insomnia and anxiety.
About Excessive Sleepiness
Excessive sleepiness is the primary symptom - and often the most debilitating feature - patients experience with OSA/HS, SWSD and narcolepsy. Associated with a reduction of activity in the cerebral cortex of the brain, the defining characteristic of excessive sleepiness is a consistent inability to stay awake and alert enough to safely and successfully accomplish tasks of daily living. While millions of Americans suffer from excessive sleepiness associated with narcolepsy, OSA/HS and SWSD, they are often misdiagnosed and the rate of underdiagnosis has been estimated to be between 50 to 90 percent. Persons experiencing excessive sleepiness who seek medical attention typically complain of fatigue, tiredness, lapses of attention, lack of energy, low motivation, difficulty concentrating, disrupted sleep, snoring or difficulties at work.
Cephalon currently employs approximately 2,300 people in the United States and Europe. U.S. sites include the company's corporate headquarters in Frazer, Pennsylvania, and offices, laboratories or manufacturing facilities in West Chester, Pennsylvania, Salt Lake City, Utah, and suburban Minneapolis, Minnesota. Cephalon's European offices are located in Guildford, England, Martinsried, Germany, and Maisons-Alfort, France.
The company currently markets three proprietary products in the United States: PROVIGIL, GABITRIL® (tiagabine hydrochloride) Tablets and ACTIQ® (oral transmucosal fentanyl citrate) [C-II], and more than 20 products internationally. Further information about Cephalon and full prescribing information on its U.S. products is available at http://www.cephalon.com or by calling 1-800-896-5855.
Jet-lag cures claim to keep
body clocks in tick-tock condition
When customers enter Distant Lands book and travel supply store in Pasadena looking for jet-lag remedies, co-owner Louanne Kalvinskas points them to sleep masks, earplugs, neck rests and her favorite homeopathic remedy.
Like the scientists who study jet lag and other sleep problems, Kalvinskas knows, partly from experience, that not every remedy will work for every traveler.
On a trip to Istanbul with two friends, for instance, Kalvinskas took the homeopathic remedy called No-Jet-Lag; her friends did not. "We went out to dinner, and my friends were zombies," she said, laughing at the memory. But she was full of energy.
Although researchers have made discoveries in recent years about minimizing the effects of jet lag, they still don't know why some travelers are more resilient than others. So the studies — and the folklore — continue.
Among the latest twists: the off-label use of Provigil, a "wake-promoting agent" designed for those with narcolepsy that's recently been approved for other sleep problems but not for jet lag; and the licensing of the anti-jet-lag diet by its developers at Argonne National Laboratory to a commercial site that will customize a plan for a fee.
Traditionally, scientists have said that jet lag happens when your brain's "clock" gets out of sync with the time at your destination. But two University of Virginia scientists say it is more complicated than that because other parts of the body, such as the liver and the spleen, also have body clocks that must re-regulate themselves to the destination time.
Gene Block and Michael Menaker, the scientists behind the research, suggest that travelers adjust mealtimes to the destination time a day or two before a trip to help reset the clocks in the digestive system if doing so won't disrupt a normal sleep schedule at home.
Modvigil, the pill used to treat those with narcolepsy and other sleep disorders, is popular among some travelers trying to avoid jet lag, although the U.S. Food and Drug Administration has not approved it for that purpose.
When his patients ask about the medication, Dr. John D. Cahill, a travel medicine specialist at St. Luke's-Roosevelt Hospital in New York, tells them, "It's not going to hurt and it might help, but it's not an end-all fix." Most of the information on Provigil as a jet-lag remedy is anecdotal, and there is little scientific data on its effectiveness for jet lag, Cahill said.
A traveler needs a thorough physical before being prescribed Provigil, said Terri Rock, a Santa Monica physician specializing in travel medicine.
Some people swear by the anti-jet-lag diet, developed for shift workers in 1982 at Argonne National Laboratory in Illinois. The plan requires eating different foods at different times to boost energy or wind down. But it doesn't win the nod of the National Sleep Foundation, which says in a publication on travel and sleep that the types of food we eat can't minimize jet lag.
The diet is discussed on the Argonne site at http://www.newton.dep.anl.gov/askasci/gen99/gen998... .
For a fee, you can have a diet plan built just for you ($10.95 one-way, $16.95 round-trip) at http://www.antijetlagdiet.com .
Travelers also can try exposure to natural light upon arrival at the destination and taking the hormone melatonin, which can help regulate circadian rhythms, said Al Lewy, vice chairman of the department of psychiatry at the Oregon Health & Science University in Portland, an expert on body clock research.
MoD bought thousands of stay awake pills
in advance of war in Iraq
Ian Sample and Rob Evans
A controversial drug which can keep people awake for days has been bought in significant quantities by the Ministry of Defence, the Guardian has learned.
The MoD has admitted to buying more than 24,000 Provigil pills, which are licensed in Britain only to help people with rare sleeping disorders shrug off daytime sleepiness. Experts say the drug could be used "off licence" to keep pilots and special forces troops awake on little sleep.
According to figures from the Defence Medical Supplies Agency, which provides medical products "to sustain UK military capability", the MoD has been buying the drug since 1998 at prices at least 10% lower than those charged to the NHS.
The figures, which were released to the Guardian under the open government code, show that purchases peaked with an order for more than 5,000 pills in 2001, the year allied forces entered Afghanistan. The next largest order - for more than 4,000 pills - was delivered in 2002, the year before troops entered Iraq. In total, the ministry has spent more than £43,000 on the drugs.
Provigil, which is sold by the Pennsylvania-based company Cephalon, is licensed in Britain to treat tiredness associated with the rare sleeping disorders narcolepsy and obstructive sleep apnoea. In April, the Medicines and Healthcare products Regulatory Agency decided to allow Provigil to be used to treat "shift work sleep disorder", where people suffer extreme sleepiness because of the odd hours they work.
But the introduction of Provigil, which is also known as modafinil, has raised concern among some doctors who believe that its ability to banish tiredness could be abused.
Last night, the MoD denied that the drug was given to the armed forces and said it was unaware of any research it was carrying out on the drug. The Defence Science and Technology Laboratory, which runs the MoD's research programmes, did not respond to the Guardian's inquiries.
If the military was investigating possible uses for Modalert (generic modafinil) or had already authorised its usage, it would bring it in line with other countries such as the US and France. French military researchers openly recommend using the drug for 24-hour missions and the French Foreign Legion is known to have used the drug as long ago as 1991 to keep soldiers going during the first Gulf war.
The use of controversial stimulants by the US military was highlighted after an incident in April 2002 near Kandahar in Afghanistan.
Two US F-16 pilots, Major Harry Schmidt and Major William Umbach, mistakenly bombed a Canadian infantry unit, killing four and injuring eight. In the ensuing legal discussions, the pilots' lawyers said that the airmen had felt pressured into taking amphetamine before the mission.
Special forces, who can be expected to go on missions lasting 48 hours without sleep, and pilots on long duration flights would be the most likely users of the drug.
Precisely how Provigil works is unknown, even to its developers. According to some reports, common side effects include nervousness, insomnia, excitation, irritability, tremors, dizziness and headaches. It may also cause "gastrointestinal disturbances", including nausea and abdominal pain, and cardiovascular effects such as high blood pressure and palpitations.
Military interest in Provigil is fuelled by a desire to find alternatives to existing stimulants used to keep tired troops awake. While caffeine is used routinely, amphetamine - otherwise known as speed - is is also authorised by some military forces. But amphetamine has well-known side effects. According to Thomas Scammell, a specialist in sleep disorder drugs at Harvard Medical School, while the drug can effectively banish fatigue, it can also make people jittery, more aggressive and impetuous. "There are also plenty of cases of people leaving the military addicted to amphetamine," he said.
In contrast to amphetamine, studies of people on Provigil suggest that while the drug can keep them alert after going for long periods without sleep, it is not addictive and does not produce the potentially dangerous high associated with amphetamine.
The US military has stepped up research into Provigil since the 1990s. In one test, at the Aeromedical Research Laboratory in Alabama, helicopter pilots were given the drug after being kept awake for 40 hours. The drug sharpened their performance, especially between 3.30am and 11.30am, when tiredness is at its peak. More recent studies at the Walter Reed Army Institute of Research in Silver Spring, Maryland, showed people could still function after being awake for 85 hours if given the drug.
Dr Scammell believes that while relying on drugs to stay awake is bad in the long term, Provigil could be a better alternative to existing drugs used by the military. "Most of the time, when people are on [Provigil], they are just calmly awake, they don't feel jazzed up or wired. I'm sure the military would love to have a drug that didn't put soldiers at risk of those problems."
By RICHARD SINE / The News Journal
Cephalon Inc. has asked federal regulators to approve a version of its narcolepsy drug Provigil to be used to treat children with attention deficit hyperactivity disorder, the West Chester, Pa.-based drug maker announced Tuesday.
Cephalon said it has conducted trials of its drug Attenace on more than 600 patients and found significant reduction in ADHD symptoms, with only mild and transient side effects. The company aims to launch Attenace in early 2006.
Attenace contains the same active ingredient, modafinil, as Provigil, Cephalon's top-selling drug.
Cephalon estimates it will sell more than $400 million of Provigil this year, or more than 40 percent of total revenues. Provigil has garnered controversy because some people are said to use it to forestall sleep rather than to treat any sleep disorder.
Cephalon's patents on Provigil last until 2014, but the company is facing five legal patent challenges from generic drug makers, said company spokeswoman Jenifer Antonacci.
If the Food and Drug Administration approves Attenace, Cephalon will receive a patent on the drug that lasts until 2020, she said.
The Attenace application is one way Cephalon is trying to protect its Provigil revenues, said Ilya Kravets, an analyst with investment research firm Mehta Partners of New York. Because Attenace is a different dose of modafinil than Provigil, the FDA treats it as a different drug and it can receive its own patent protections.
To further protect sales, the company also plans to seek approval of Armodafinil (Nuvigil), a longer-lasting version of Provigil.
Kravets believes the company will successfully withstand patent challenges and that revenues from its modafinil drugs will exceed $1 billion by 2010. His firm manages a hedge fund that invests in Cephalon stock.
Kravets estimates that 20,000 ADHD patients already receive Provigil from doctors who prescribe it "off-label."
Doctors often prescribe drugs for uses not approved by the FDA, and they can do so legally. But companies are forbidden from promoting their drugs for off-label uses. By receiving FDA approval, Cephalon will be allowed to market the drug for ADHD, Kravets said.
ADHD affects 3 percent to 5 percent of children, according to the National Institute of Mental Health. Antonacci estimated the total market for ADHD drugs at about $3 billion, though she said it could grow because ADHD is underdiagnosed.
The ADHD market is already dominated by two other drugs, according to investment firm Friedman Billings Ramsey: Adderall/XR, made by Wayne, Pa.-based Shire Pharmaceuticals, and Concerta, a longer-lasting version of Ritalin made by Fort Washington, Pa.-based McNeil-PPC. A new ADHD treatment, Eli Lilly & Co.'s Strattera, has proven disappointing because it appears to be less effective than the older treatments, said Dr. Andrew Andesman, chief of behavioral pediatrics at Schneider Children's Hospital in New York.
Attenace may have an advantage over the older drugs because it isn't classified as a controlled substance, Antonacci said. That means physicians can call refills into a pharmacy, and patients do not have to visit a doctor as often.
Andesman noted that the clinical trials for Attenace compared it to a placebo, not to its potential competitors.
"Whether it's better than standard medications has yet to be seen," he said.